The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: A multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia

Judd Walson, James Berkley, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahid, Md Amran Gazi, Ali Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere, Christina L. Lancioni, Emily Yoshioka, Mohammod Jobayer Chisti, Moses Mburu, Moses Ngari, Narshion Ngao, Bonface Gichuki, Elisha OmerWilson Gumbi, Benson Singa, Robert Bandsma, Tahmeed Ahmed, Wieger Voskuijl, Thomas N. Williams, Alex Macharia, Johnstone Makale, Anna Mitchel, Jessica Williams, Joe Gogain, Nebojsa Janjic, Rupasri Mandal, David S. Wishart, Hang Wu, Lei Xia, Michael Routledge, Yun Yun Gong, Camilo Espinosa, Nima Aghaeepour, Jie Liu, Eric Houpt, Trevor D. Lawley, Hilary Browne, Yan Shao, Doreen Rwigi, Kevin Kariuki, Timothy Kaburu, Holm H. Uhlig, Lisa Gartner, Kelsey Jones, Albert Koulman

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.

Original languageEnglish
Article number77
JournalGates Open Research
Volume6
DOIs
Publication statusPublished - 2022

Keywords

  • Case-Cohort
  • Children
  • LMIC
  • Mortality
  • Omics
  • Systems Biology

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